This invention relates to blood glucose testing in critically ill patients. The need for a convenient and easily applied method of glucose monitoring in the Intensive Care Unit became evident after the landmark study of Van den Berghe and colleagues published in the Nov. 8, 2001 issue of The New England Journal of Medicine. 
This paper demonstrated an overall reduction in ICU (intensive Care Unit) patient mortality of 34% when blood glucose was kept in the 80 to 110 mg per deciliter range. Samples were taken from an arterial line at 1 to 4-hour intervals and sent to the hospital lab for analysis. In the intensive therapy group, an insulin infusion was started if blood glucose exceeded 110 mg per deciliter and was adjusted to maintain normal blood glucose levels. A virtual flood of articles have since appeared and confirm improved outcomes in the treatment of various critical conditions including infection, stroke, in patients undergoing coronary bypass surgery, and in the treatment of myocardial infarction in both diabetic and non-diabetic patients. One study showed greatly improved outcomes when diabetics were monitored and treated intensively with insulin in the hospital for three days prior to undergoing coronary bypass surgery.
Intensive treatment with insulin requires knowledge of patient blood sugar levels which presently involves obtaining either an arterial or a venous blood sample or pricking the patient's finger from time to time to obtain a capillary blood sample. Capillary samples are placed on a strip and read using a home-type glucose meter. All of these methods require considerable nurse or technician time. In the U.S. at present only 20% to 30% of patients in the ICU have arterial lines. Many patients, especially non-diabetics, find repeated finger sticks objectionable. Furthermore, intermittent blood samples may not be done often enough to give an accurate picture of blood sugar levels.
Attempts have been made in the past to automatically monitor blood analytes, especially blood gases. Most method have involved reversing the direction of blood flow in an infusion line so that blood is pulled out of the patient's circulation at intervals, analyzed and then re-infused back into the patient by changing the direction of flow. This method was possibly first described by Clark in U.S. Pat. No. 3,910,256 who used saline flushes between samples and whose method had means for detecting air in the blood which resulted in an alarm and shutting down the infusion.
Parker in U.S. Pat. No. 4,573,968 describes a system in which an infusion pump reverses direction to draw a patient blood sample through a catheter into contact with one or more electrochemical sensors. A compact cassette near the patient carries the sensors.
Wong and Associates in U.S. Pat. Nos. 5,165,406; 5,758,643 and 5,947,911 describe a system again using a peristaltic pump to move infusion fluid and blood back and forth through the system. Sensing is done by a cassette which is placed on the patient's forearm.
In U.S. Pat. No. 5,758,643 Wong and Associates determine the arrival of blood in the area of the sensors by reading the signals from the sensors, themselves, and ascribe particular importance to a calcium sensor. The system is programmed to activate an alarm and switch off the infusion pump if the arrival of the patient's blood sample in the area of the sensors has not been detected by a predetermined time. In U.S. Pat. No. 5,947,911 Wong's group describes methods for reducing the volume of the purging fluid following the taking of a sample.
All of the systems mentioned have a level of complexity which makes manufacturing of the devices expensive and their practical application difficult and time consuming. Via Medical, now a division of International Biomedical of Austin, Tex., manufactures and sells the device designed by Wong and Associates. It uses a large patient monitor and a cassette-type analyzer on the patient's forearm. Cost of the disposables for each patient use is approximately $300 for either blood gases or blood glucose. Set-up time is fifteen to twenty minutes.
What is clearly needed is a system for hospitalized patients which is affordable and uncomplicated. The present invention eliminates the difficulties and complexities of previously described devices using a novel method of blood sampling located close to the catheterized artery or vein.
A problem encountered in reversing an infusion line for sampling is determining how much blood should be withdrawn in order to be certain that pure undiluted blood is in contact with the sensor. This problem is discussed in U.S. Pat. No. 5,758,643 by Wong and Associates who attempt to solve the problem with the sensors themselves and particularly a calcium sensor which presumably will register a blood calcium in a normal range when undiluted blood has reached the sensing area. This method, while fairly satisfactory, may be somewhat inaccurate unless the patient's actual blood calcium level is exactly known. Also, there may be some delay between the time an undiluted sample reaches the sensing area and the time that a normal value is registered by the sensor and transmitted to the monitor which contains the pump. As a result, an unnecessarily large amount of blood may be withdrawn prior to stopping the peristaltic pump which is pumping in a retrograde manner to remove blood from the patient's catheter.
The present invention discloses a novel method of halting the withdrawal of blood at the proper time so that a pure undiluted sample is presented to the sensor and ensures that no more than the necessary amount of blood is withdrawn. In the method to be described, at least one, and for optimum performance two, LED/photodetector pairs are placed adjacent to the sampling chamber. In the present invention, the change from clear fluid to blood within the sampling chamber will cause a fairly sudden drop in the amount of light crossing the chamber since red cells will block considerable light in contrast to ordinary infusion fluid which is clear. The area of transition will be smeared out to a greater or lesser extent depending on the speed of the infusion and the size of the catheterized blood vessel. If the infusion was rapid, for example several hundred milliliters per hour, the transition area may extend for 10 to 20 cm up the blood vessel. If very little fluid was being infused, the withdrawal of a fluid column of just a few centimeters may suffice to place a pure blood sample into the sampling chamber. The disposable device, with an LED/photodetector pair at each end of the sampling chamber, can readily detect when pure or undiluted blood fills the entire chamber because light reaching the photodetectors will be equivalent. It is at this moment, when equal amounts of light are received by the photodiodes, that the reverse motion of the peristaltic pump inside the bedside monitor can be stopped and the blood level of glucose tested.
Following testing, the peristaltic pump is again run in the normal forward direction to resume the infusion at the rate set by the caregiver.
The present invention contains no expensive parts and can be made economically to allow wide use of the invention among critically ill hospitalized patients. The disposable test unit is relatively small and can be worn with comfort by the patient on the mid-forearm with the vessel catheter crossing the wrist to be inserted, in most cases, in a small vein on the back of the hand. Catheters of this type are commonly used for infusion lines and can be inserted by virtually all medical personnel who care for the critically ill.
The catheter may be inserted elsewhere as well and the device can be used with arterial lines or central venous catheters. It is particularly useful in the latter case since dilution of venous blood in a central line may extend quite high up the arm. Regardless of the amount of dilution, the invention will be able to discern when a pure blood sample has reached the sampling chamber.
The disposable test unit is built up from four layers of plastic and, when the layers are joined in final assembly, the device measures approximately 56 mm×30 mm×11 mm (2.25×1.25×0.440 inches). The layers are each 2.5 to 3.0 mm thick and allow features such as the sampling chamber to be molded into the thin layers of plastic. The flex circuit carrying the glucose sensor is located between layers 2 and 3. The flex circuit carrying the LEDs is mounted between layers 1 and 2, and the flex circuit carrying the photodetectors is mounted between layers 3 and 4. The four layers are welded together ultrasonically to produce in the final assembly a water tight hermetically sealed device.
The glucose sensing area of the disposable device contains a glucose oxidase electrode with an active area of about 25 square millimeters. The glucose electrode is affixed to the distal area of the flex circuit and is covered by a thin polyurethane membrane which prevents cells and proteins from interfering with the action of the enzyme. An advantage of sampling intermittently, for example once every five minutes, is that during the period of ordinary fluid infusion, the membrane is cleared of cells and proteins which may have temporarily lodged on the membrane but are washed off by the infusion fluid between tests so that the possibility of membrane clogging by proteins or cells is greatly reduced. A suitable glucose oxidase electrode for such a flex circuit is made by Conductive Technologies of York, Pa.
The disposable test unit is provided on its front surface with a male Luer fitting to take the female end of a polyethylene blood vessel catheter. The infusion line and electric cable carrying the electric leads are attached to the opposite face of the test unit with the infusion line being terminated at a drip chamber which inserts into a standard IV fluid bag. The cable carrying the electronic leads from the various flex circuits attached to an appropriate receptacle on the monitor.
The infusion line is provided near its upper extremity with a short segment of soft silicone tubing to facilitate its use with a peristaltic pump. A door at the front of the monitor allows the caregiver to place the silicone portion of the infusion tubing next to the pump roller, and closure of the door on the front of the monitor locks the tubing in place against the roller wheel of the pump. A small peristaltic pump suitable for this application is made by Watson-Marlow Bredel of Commerce, Colo.
Calibration can be accomplished daily or as often as needed by stopping the pump and injecting calibration fluid into the sampling chamber through a Luer-activated valve close to the chamber. During calibration, the glucose electrode reads the glucose value of the solution and, if necessary, resets the electronic look-up table in the monitor to reflect the known value of the calibration solution.
A primary object of the invention is to provide a low cost, disposable and simple device for automatically monitoring blood glucose levels in hospitalized patients.
A further object of the invention is to provide a simple but yet reliable system for determining when an undiluted sample of blood is present in a test chamber prior to testing the sample for its blood glucose level.
Other objects and advantages will become apparent from the following description and drawings.